2014 biotech showcase presentation, january 13, 2014
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TRANSCRIPT
LEADING REGENERATIVE MEDICINE
This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced Cell Technology Inc”, or “the Company”) salient business characteristics.
The information herein contains “forward-looking statements” as defined under the federal securities laws. Actual results could vary materially. Factors that could cause actual results to vary materially are described in our filings with the Securities and Exchange Commission.
You should pay particular attention to the “risk factors” contained in documents we file from time to time with the Securities and Exchange Commission. The risks identified therein, as well as others not identified by the Company, could cause the Company’s actual results to differ materially from those expressed in any forward-looking statements. Ropes Gray
Cautionary Statement Concerning Forward-Looking Statements
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Renewable Pluripotent Stem Cell Platform
Renewable Pluripotent Stem Cells RPE
Photo-receptors
Ganglion Nerve Cells
Corneal Cells
MSC
RBC
Dry AMD Stargardt’s Disease MMD
Macular Degeneration Retinitis Pigmentosa Diabetes-related blindness.
• Glaucoma • Diabetic eye
disease
Corneal diseases Corneal Injuries
Differentiated MSC Products - Renewable Source - Highly Potent relative to adult MSC
Autoimmune Diseases Inflammatory Diseases Wound Healing
Secreted Neuroprotective Biological Agent(s)
Thombocytopenia Wound Healing Engineered Platelets
- release therapeutic upon activation
Platelets
Wound Healing Transfusion Anemia
ES iPS next gen
A Robust Clinical and
Preclinical Pipeline
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Pre-clinical/ in vitro
POC – Animal Studies IND Approved Phase I Phase II Phase III Approval
Dry AMD
SMD
MMD
Photo-receptors
Ganglion Neurons
Cornea
Mesenchymal Stem Cells
Platelets
Robust Development Pipeline Provides Multiple Opportunities to Commercialize and Partner
First Priority Based On Current Funding
Advance to POC or Phase I and Partner
Potential Gov’t Funding
Oph
thal
mol
ogy
Prog
ram
s
Based on POC results, pursue appropriate funding and collaborations
Retina
Structure of the Retina
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Life Support to Photoreceptors
Provides nutrients and growth factors • photoreceptors see no blood
Recycles Vitamin A • maintains photoreceptor excitability
Detoxifies photoreceptor layer
Maintains Bruch’s Membrane • natural antiangiogenic barrier • immune privilege of retina
Absorbs stray light / protects from UV
RPE Layer has multiple
critical roles in the
health and function
of photoreceptors and the retina as a whole.
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Life Support to Photoreceptors
Failure of RPE cells results in many degenerative diseases Stargardt’s disease Myopic Macular Dystrophy Age-related macular degeneration (AMD)
Age-Related Macular Degeneration will Soon Take on Aspects of an Epidemic
60%
50%
40%
30%
20%
10%
50-59 40-49 60-69 70-79 80+ Age
Intermediate AMD Late AMD
% P
reva
lenc
e (U
.S.)
Data from http://www.nei.nih.gov/eyedata/ and U.S. Census Bureau Publication “65+ in the United States”, P23-209
Exponential rise in prevalence and incidence rates with age, with prevalence rates of late AMD quadrupling per decade
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Age-Related Macular Degeneration will Soon Take on Aspects of an Epidemic
Data from http://www.nei.nih.gov/eyedata/ and U.S. Census Bureau Publication “65+ in the United States”, P23-209
Exponential rise in prevalence and incidence rates with age, with prevalence rates of late AMD quadrupling per decade
60%
50%
40%
30%
20%
10%
50-59 40-49 60-69 70-79 80+ Age
Intermediate AMD Late AMD
% P
reva
lenc
e (U
.S.)
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Age-Related Macular Degeneration will Soon Take on Aspects of an Epidemic
Data from http://www.nei.nih.gov/eyedata/ and U.S. Census Bureau Publication “65+ in the United States”, P23-209
133.7 142.2 173.4 202.7 207.4 205.5 37.4 52.9
64.8 81.9 105.3 121
80+ 65-79
2000 2010 2020 2030 2040 2050
Developed Countries
“macular degeneration will soon take on aspects of an epidemic” - former Director of the National Eye Institute Dr Carl Kupfer
There are currently >30 Million American and European AMD patients. This is projected to exceed 50 Million patients by 2025
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Wong et al. Lancet January 2014 The projected number of people with age-related macular degeneration in 2020 is 196 million, increasing to 288 million in 2040.
Cell Therapy for RPE, Achievable by a Small Company
Small dosage size • less than 200K cells
Immune-privileged site • minimal immunosuppression
Ease of administration • no separate device approval
Unique measuring and observation environment • measurable endpoints
Significant unmet medical need
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GMP process for differentiation and purification of RPE – Virtually unlimited supply from stem cell source – Optimized for large scale manufacturing
Ideal Cell Therapy Product – Centralized Manufacturing – Robust Release Assays – Simple Handling
GMP Process
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ACT Cleanroom Suite
Product Cold Chain is Easily Scaled for Global Sales
A single 6-well plate can generate 50-
100 doses
January 2013: FDA approved additional 4 patient “better vision” cohorts in each trial.
For Cohort 2a – can enroll patients with vision as good as 20/100.
Cohort 1
50K Cells Cohort 2
100K Cells Cohort 3
150K Cells Cohort 4
200K Cells
Cohort 2a
100K Cells
First Treatments informed a more aggressive strategy to treat “better vision” cohort, could lead to broader label and/or earlier approval
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Jules Stein (UCLA)
Mass Eye & Ear Infirmary
Wills Eye Institute
Bascom Palmer Eye
Institute
Moorfields Eye
Hospital
Edinburgh Royal
Infirmary
World renowned leadership to help us navigate the clinical path and ultimately support market launch
Clinical Trials being led by World Leaders in Ophthalmology
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Surgical Overview
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Procedure: • 25 Gauge Pars Plana Vitrectomy • Posterior Vitreous Separation • Subretinal hESC-derived RPE cells
injection • Bleb Confirmation • Day Surgery/Sedation only
IND Approved
50% Patient Enrollment
100% Patient Enrollment
U.S. – Dry AMD
U.S. – SMD
U.K. – SMD
U.S. – MMD
12/16 patients treated
11/16 patients treated
9/12 patients treated
Enrolling – 12 patients total
Current Enrollment
32 Patients Treated to Date
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• No Adverse Events • Persistence of cells • Impact on Acuity
Recorded functional visual improvements in majority of patients.
• Increased letters on ETDRS Charts
• Color perception • Contrast • Low light vision
Phase I Trials Exceeding Expectations – no adverse events and persistence of cells
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Preliminary Results
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Recorded functional visual improvements in both patients.
• SMD Patient: Best corrected visual acuity improved from hand motions to 20/800 and improved from 0 to 5 letters on the ETDRS visual acuity chart in the study eye.
• Dry AMD Patient: Vision improved in the patient with dry age-related macular degeneration (21 ETDRS letters to 28).
32 Patients - up to 2 years of follow-up visits
• Measurable Improvements in Visual Acuity for Majority of Treated Patients
• Gains in visual acuity generally persist
SMD Patient #1
Visual acuity gains have persisted for more than 2 years
Expanding Clinical Programs
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Myopia creates a higher risk of permanent vision loss due to Myopic Macular Degeneration (MMD)
• Severe near-sightedness causes elongation of the eyeball -- which can cause fissures in RPE layer.
January 2013 - FDA Approved MMD Phase I/II study Jules Stein Eye Institute (UCLA) and ACT
Second Generation RPE Cell Therapy Products
By engineering the master stem cell bank used to manufacture RPE cells, the transplanted RPE cells can express
• Anti-angiogeneic agents Reduce occurrence of choroidal neovascularization (wet AMD).
• Complement factor D, Factor C5 and/or Factor C3 Inhibitors Activation of alternative complement pathway implicated in disease progression for certain patients
• Anti β-amyloid agents Drusen deposits resemble amyloid deposits.
• Anti-Inflammatory agents IL-1, IL-2, IL-3, and TNF-α antagonists Recombinant Lipocortin – a potent anti-inflammatory protein
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Intellectual Property – RPE Program Dominant Patent Position for Treating Retinal Degeneration
• Broad Coverage for Manufacturing RPE Cells • Broad protection of pharmaceutical preparations
Covers both RPE cell suspensions and scaffolded RPE layers. • RPE Cells derived from other pluripotent stem cells – e.g., iPS cells
o Careful Consideration of Literal Scope o Preservation of Doctrine of Equivalents o Constantly Mining Existing Filings o Vigilantly Filing on Improvements
Keeping our IP Lawyers
on their toes
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Neurosensory Retina Photoreceptor and Ganglion Progenitor Cells
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Pluripotent Stem Cell
Eye Field Stem Cell
RPE
Photoreceptor
Ganglion
ACT has developed proprietary methods for deriving various cell
types of the retina
• Defined culture conditions • High yield from hESC • Homogeneous and highly
pure preparations
Ocular Program – Retinal Neural Progenitors
Sub-retinal injection of Photoreceptor Progenitor cells promoted functional of recovery photoreceptor function in animal models of photoreceptor loss
Observed incorporation of human photoreceptor cells into Outer Nucleated Layer
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Photoreceptor Progenitor Cells
1 week after subretinal transplantation 3 week after subretinal transplantation
Preliminary data suggests cells secrete soluble and potent neuroprotective agent(s)
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Photoreceptor Progenitor Cells
In addition, systemic injection of progenitor cells had the surprising result of providing neuroprotective activity
Evidence for Secreted Neuroprotective Agent
a-wave b-wave
PhPr, 2 mo PhPr, 2 mo
PhPr, 1 mo PBS, 1 mo PBS, 2 mo
PhPr, 1 mo PBS, 1 mo PBS, 2 mo
Systemically delivered Photoreceptor Progenitor cells reversed the progression of photoreceptor degeneration – and promoted regeneration of both Rods and Cones
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Mesenchymal Stem Cell Program
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Mesenchymal Stem Cells in Therapy
Self External Autoimmune Diseases Rheumatoid Arthritis, Psoriasis,
Multiple Sclerosis, Crohn’s disease, Type I Diabetes, Lupus
Allergic Reaction Asthma, eczema,
sinusitis
Immune Over-reaction
Balanced Immune System
Autoimmune Disease Prevalence • At least 80 disease affecting every organ system • Americans spend over $100B each year in total
healthcare costs associated with autoimmune disease • In the U.S., 14.7-23.5M people (5%-8%) (for comparison: heart disease (22M), Cancer (9M)
A rapidly growing health issue (% growth)
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Suppressing Immune Responses gives rise to Therapy
Promising therapeutic potential for treating autoimmune and inflammatory diseases.
However, adult-derived MSCs are limited by replicative capacity
Mesenchymal stem cells (MSCs) suppress disease-causing immune responses
ACT Proprietary Process • Manufacture MSC’s from hES and iPS Cell Banks
• Virtually inexhaustible source of starting material • Use Single Master Cell Bank • Less labor-intensive
A further differentiating feature…
Our MSC’s are substantially more potent than current sources of cells
ACT’s Breakthrough – Inexhaustible Supply of Very Potent MSC’s
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Gary Rabin –CEO
Edward Myles – CFO and EVP of Corp Development
Dr. Matthew Vincent, Ph.D. – Dir., Business Development
Dr. Robert Lanza, MD – Chief Scientific Officer
Dr. Irina Klimanskaya, Ph.D. – Dir., Stem Cell Biology
Dr. Shi-Jiang (John) Lu, Ph.D. – Senior Director of Research
Eddy Anglade, M.D. – EVP, Clinical Development
Dr. Roger Gay, Ph.D. - Senior Director of Manufacturing
Proven business leaders who can develop and implement corporate
strategy and monetize assets to maximize shareholder value
World-renowned scientific thought leaders pushing the cutting edge of
science to develop important therapies
Deep experience in clinical development programs for ophthalmology drug products from
early through late-and post-marketing stages
GMP manufacturing to ensure the highest quality products are delivered to our patients
An Experienced and Dedicated Management Team
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Michael Heffernan CEO – Collegium Pharmaceuticals
Robert S. Langer, Sc.D. Institute Professor, MIT
Zohar Loshitzer CEO – Presbia, Inc., & Principal in Orchard Capital
Greg Perry EVP & CFO – InVivo Therapeutics
Alan C. Shapiro
Finance Professor and Chairman of the Department of Finance and Business
Economics (retired) – University of Southern California
Gary Rabin CEO – Advanced Cell Technology
A World-Class Board of Directors
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Thank you For more information, visit www.advancedcell.com